A theory of group selection.

A theory of group selection. In organisms possessing a dispersal phase the processes of mating, competition, feeding, and predation are often carried out within "trait-groups," defined as populations enclosed in areas smaller than the boundaries of the deme. A simple model shows that this can lead to the selection of "altruistic" traits that favor the fitness of the group over that of the individual. The extent of group selection that occurs depends mainly on the variation in the composition of genotypes between trait-groups. The traditional concepts of group and individual selection are seen as two extremes of a continuum, with systems in nature operating over the interval in between.


Nonrandom chromosomal abnormalities in hematologic disorders of man. A nonrandom pattern of chromosomal abnormalities occurs in bone marrow cells obtained from patients with hematologic disorders who have an abnormal karyotype involving a C group chromosome. An additional number 8 chromosome is the most common abnormality, found in more than one-half of the patients studies. An additional number 9 chromosome and the loss of all or part of a number 7 are abnormalities that occur more often than might be expected by chance. It is proposed that specific human chromosomal abnormalities may be related to different specific etiologic agents.


Bovine factor X1 (Stuart factor). Primary structure of the light chain. The amino-acid sequence of the light chain of bovine factor X1 is presented. The sequence of 112 of the 140 residues was determined automatically on fragments produced by specific cleavage of arginyl, glutamyl, tryptophanyl, and asparaginyl-glycine bonds. The remainder was determined by conventional procedures. The amino-terminal sequence of the light chain is homologous with the amino-terminal region of bovine prothrombin and, like the latter, appears to contain several residues of a recently discovered unusual amino acid, lambda-carboxy-glutamic acid. The role of this amino acid in the calcium-binding ability of factor X and prothrombin is discussed.


A nonidentifiability aspect of the problem of competing risks. For an experimental animal exposed to k greater than 1 possible risks of death R1, R2, ..., Rk, the term i-th potential survival time designates a random variable Yi supposed to represent the age at death of the animal in hypothetical conditions in which Ri is the only possible risk. The probability that Yi will exceed a preassigned t is called the i-th net survival probability. The results of a survival experiment are represented by k "crude" survival functions, empirical counterparts of the probabilities Qi(t) that an animal will survive at least up to the age t and eventually die from Ri. The analysis of a survival experiment aims at estimating the k net survival probabilities using the empirical data on those termed crude. Therorems 1 and 2 establish the relationship between the net and the crude probabilities of survival. In particular, Theorem 2 shows that, without the not directly verifiable assumption that in their joint distribution the variables Y1, Y2, ..., Yk are mutually independent, a given set of crude survival probabilities Qi(t) does not identify the corresponding net probabilities. An example shows that the results of a customary method of analysis, based on the assumption that Y1, Y2, ..., Yk are independent, may have no resemblance to reality.


Evidence for de novo production of self-replicating and environmentally adapted RNA structures by bacteriophage Qbeta replicase. Highly purified coliphage Qbeta replicase when incubated without added template synthesizes self-replicating RNA species in an autocatalytic reaction. In this paper we offer strong evidence that this RNA production is directed by templates generated de novo during the lag phase. Contamination of the enzyme by traces of RNA templates was ruled out by the following experimental results: (1) Additional purification steps do not eliminate this RNA production. (2) The lag phase is lengthened to several hours by lowering substrate or enzyme concentration. At a nucleoside triphosphate concentration of 0.15 mM no RNA is produced although the template-directed RNA synthesis works normally. (3) Different enzyme concentrations lead to RNA species of completely different primary structure. (4) Addition of oligonucleotides or preincubation with only three nucleoside triphosphates affects the final RNA sequence. (5) Manipulation of conditions during the lag phase results in the production of RNA structures that are adapted to the particular incubation conditions applied (e.g., RNA resistant to nuclease attack or resistant to inhibitors or even RNAs "addicted to the drug," in the sense that they only replicate in the presence of a drug like acridine orange). RNA species obtained in different experiments under optimal incubation conditions show very similar fingerprint patterns, suggesting the operation of an instruction mechanism. A possible mechanism is discussed.


Slow evolutionary loss of the potential for interspecific hybridization in birds: a manifestation of slow regulatory evolution. Birds have lost the potential for interspecific hybridization slowly. This inference emerges from protein comparisons made on 36 pairs of bird species capable of hybridization. Micro-complement fixation tests show that hybridizable pairs of bird species differ by an average of 12 units of albumin immunological distance and 25 units of transferrin immunological distance. As these proteins evolve at a known and rather steady rate, it is inferred that the average hybridization species pair diverged from a common ancestor about 22 million years ago. The corresponding period for frog species pairs capable of hybridization is about 21 million years, while for hybridizable placental mammals it is only 2 to 3 million years. Thus birds resemble frogs in having lost the potential for interspecific hybridization about 10 times as slowly as have mammals. Birds have also been evolving very slowly at the anatomical level, particularly within the last 25 million years, according to Simpson, Romer, and many other vertebrate zoologists. In this respect they resemble frogs and differ from placental mammals, which have been undergoing unusually rapid anatomical evolution. Chromosomal evolution is also thought to have proceeded very slowly in both birds and frogs, relative to mammals. The above observations are consistent with the hypothesis that evolutionary changes in regulatory systems, that is, changes in the patterns of gene expression, provide the basis for both anatomical evolution and the evolutionary loss of hybridization potential.


Temperature-sensitive mutants of chemically transformed epithelial cells. The first temperature-sensitive mutants of epithelial cells transformed with chemical carcinogens have been isolated. Like the wild-type transformed parental cells, the mutants readily grow in agar suspension at 36 degrees, but in contrast to the wild type, they do not do so at 40 degrees. Detailed studies of one of these mutants, TS-223, indicate that at high temperature it also has reduced cloning efficiency in monolayer culture and a lower saturation density. Scanning electron microscopy revealed that at 40 degrees confluent cultures of TS-223 consist of a monolayer of generally flat polygonal cells, whereas 36 degrees cultures contain many patches of piled-up cells that are spherical and have rougher surface membranes. All of these cellular changes are reversible with upward or downward temperature shifts. The temperature-sensitive lesion appears to reside in a host cell gene which modulates expression of the transformed cell phenotype. These mutants may provide a useful system for elucidating the minimal biochemical changes required for expression of the transformed phenotype in epithelial cells.


Demonstration of the rapid action of pure crystalline 1 alpha-hydroxy vitamin D3 and 1 alpha,25-dihydroxy vitamin D3 on intestinal calcium uptake. The biological effects of crystalline 1alpha-hydroxyvitamin D3 and crystalline 1alpha,25-dihydroxyvitamin D3 have been compared on the intestinal uptake of calcium-45 by everted duodenal gut sacs from rachitic rats. Peak calcium-45 uptake was observed 1 hr after intravenous administration and both crystalline vitamin D2 analogs were of comparable potency. The rapid onset of calcium-45 uptake and the rapid attainment of maximal calcium-45 transport suggests a direct effect of these crystalline analogs on the mucosal membranes of the intestinal cell.


A cycle of deprotonation and reprotonation energizing amino-acid transport? Although lowering the pK2 of neutral amino acids only weakens their concentrative uptake by Ehrlich cells, the same change greatly enhances uptake of diamino acids. This effect does not arise merely from putting the distal amino group in its uncharged form, but depends on an enhanced deprotonation of the alpha-amino group. Parallel effects are seen for the transport system for basic amino acids, for which the assignment of pK values within the membrane is less ambiguous. To explain the paradoxical advantages of having the alpha-amino group protonated yet readily deprotonated, we propose that a proton withdrawn from that group is pumped over an intramembrane interval to energize amino-acid transport.


Xeroderma pigmentosum cells with normal levels of excision repair have a defect in DNA synthesis after UV-irradiation. Cells cultured from most patients suffering from the sunlight-sensitive hereditary disorder xeroderma pigmentosum are defective in the ability to excise ultraviolet light (UV)-induced pyrimidine dimers from their DNA. There is, however, one class of these patients whose cells are completely normal in this excision repair process. We have found that these cells have an abnormality in the manner in which DNA is synthesized after UV-irradiation. The time taken to convert initially low-molecular-weight DNA synthesized in UV-irradiated cells into high-molecular-weight DNA similar in size to that in untreated cells is much greater in these variants than in normal cells. Furthermore, this slow conversion of low to high-molecular-weight newly synthesized DNA is drastically inhibited by caffeine, which has no effect in normal cells. Two cell lines from classes of xeroderma pigmentosum that are defective in excision-repair show intermediate effects, with regard to both the time taken to convert newly synthesized DNA to high molecular weight and the inhibition of this process by caffeine.


Recombinant DNA molecules of bacteriophage phi chi174. Phi chi174 DNA structures containing two different parental genomes were detected genetically and examined by electron microscopy. These structures consisted of two monomeric double-stranded DNA molecules linked in a figure 8 configuration. Such DNA structures were observed to be formed preferentially in host recA+ cells or recA+ cell-free systems. Since the host recA+ allele is required for most phi chi174 recombinant formation, we conclude that the observed figure 8 molecules are intermediates in, or end products of, 1 phi chi174 recombination event. We propose that recombinant figure 8 DNA molecules arise as a result of "single-strand aggression," are stabilized by double-strand "branch migration," and represent a specific example of a common intermediate in genetic recombination.


Tay-Sachs' and Sandhoff's diseases: the assignment of genes for hexosaminidase A and B to individual human chromosomes. The techniques of somatic cell genetics have been used to establish the linkage relationships of loci coding for two forms (A and B) of hexosaminidase (EC 3.2.1.30; 2-acetamido-2-deoxy-beta-D-glucoside acetamidodeoxyglucohydrolase) and to determine whether a structural relationship exists between these forms. In a series of human-mouse hybrid cell lines, hexosaminidase A and B segregated independently. Our results and those reported by other investigators are used to analyze the proposed structural models for hexosaminidase. We have also been able to establish a syntenic relationship between the gene locus responsible for the expression of hexosaminidase A and those responsible for mannosephosphate isomerase and pyruvate kinase-3 and to assign the gene for hexosaminidase B to chromosome 5 in man. There is thus a linkage between specific human autosomes and enzymes implicated in the production of lipid storage diseases.


Human globin gene expression and linkage in bone marrow and fetal liver. During embryonic development there is a transition from embryonic and fetal to adult beta-type globin chains. The high-molecular-weight RNA found in nuclei from embryonic and adult human erythropoietic tissues, fetal liver, and bone marrow, have been investigated for the presence of gamma(fetal)- and beta(adult)-globin messenger RNA sequences by molecular hybridization. Unlike alpha- and beta-globin mRNA sequences, gamma-globin mRNA sequences are absent from both total and high-molecular-weight nuclear RNA isolated from adult bone marrow. The amount of cytoplasmic gamma-globin mRNA is proportional to the level of gamma-chain synthesis, demonstrating that translational control is not a major control mechanism in the expression of globin genes. Since the gamma-, delta-, and beta-globin genes are known to be closely linked genetically, transcriptional control can discriminate between similar gene sequences that are spatially adjacent to one another.


A mechanism to activate branch migration between homologous DNA molecules in genetic recombination. A mechanism to activate branch migration between homologous DNA molecules is described that leads to synapsis in genetic recombination. The model involves a restriction-like endonucleolytic enzyme that first nicks DNA (to produce single-strand breaks) on strands of opposite polarity at symmetrically arranged nucleotide sequences (located at ends of genes or operons). This is followed by local denaturation of the region, promoted by a single-strand-specific DNA binding protein (i.e., an unwinding protein). Hydrogen-bounding between homologous DNA molecules can then be initiated and this allows for subsequent propagation of hybrid DNA in the pathway to formation of the synapton structure.


Re-evaluation of Sepharose-insulin as a tool for the study of insulin action. The biological activity of Sepharose-insulin in different assays in vitro, e.g., stimulation of glucose oxidation, lipogenesis, and antilipolysis and activation of pyruvate dehydrogenase (EC 1.2.4.1) activity, has been investigated. According to amino acid analysis, between 270 and 330 mug (6.9-8.2 U) of insulin were coupled per ml of packed beads. Related to the total insulin content, 0.2-0.7% of the insulin was biologically active. Comparable biological activity was observed with isolated fat cells and fat pad pieces. After incubation with tissue or cells, Sepharose-insulin particles were separated by centrifugation from the medium. The clear supernatant was assayed for biologically and immunologically reactive insulin and contained soluble insulin activity. A quantitative evaluation of the soluble biological and immunological insulin activity in the supernatant accounted for the total insulin activity of Sepharose-insulin.


Steroidogenesis in rabbit preimplantation embryos. Rabbit preimplantation embryos were flushed from the reproductive tract at 24 hr (1- to 2-cell stage), 48 hr (morula), 72 hr (morula), 96 hr (blastocyst), 120 hr (blastocyst), and 144 hr (blastocyst) post coitum. At 168 hr (early postimplantation period), gestation sacs were excised, frozen, and sectioned in a cryostat. Delta5-3beta-Hydroxysteroid dehydrogenase [3(or 17)beta-hydroxysteroid:NAD(P) oxidoreductase, EC 1.1.1.51] activity was determined histochemically in whole preimplantation embryos and in sectioned postimplantation embryos. 3beta-Hydroxysteroid dehydrogenase activity began at 48 hr and was sustained through the late blastocyst stage (144 hr), with the exception of a brief drop, possibly cessation, of activity at 72 hr. There was no activity at 168 hr. Since 3 beta-hydroxysteroid dehydrogenase is a key enzyme in the metabolism of steroid hormones, its presence is strong evidence for steroidogenesis. Only 144-hr preimplantation embryos were used to determine 17 beta-hydroxysteroid dehydrogenase (estradiol-17beta:NAD 17-oxidoreductase, EC 1.1.1.62) activity, which was present, suggesting synthesis of estrogen. By means of radioimmunoassay, 144-hr preimplantation embryos were found to contain estradiol-17beta. Other authors have shown that rabbit blastocysts contain progesterone and other steroids, and these embryos can synthesize steroids from non-steroid and steroid precursors. Therefore, our results plus those of others prove that rabbit preimplantation embryos synthesize steroid hormones. Our present and previous results (with rats, hamsters, and mice) suggest that the steroid hormones synthesized by the embryo are critical for preimplantation embryogenesis and for implantation of the lbastocyst.


Ribonucleoprotein particles containing heterogeneous nuclear RNA in the cellular slime mold Dictyostelium discoideum. As in higher eukaryotes, heterogeneous nuclear RNA (HNRNA) in the cellular slime mold Dictyostelium discoideum is associated with proteins in the form of ribonucleoprotein particles. Mixing experiments with deproteinized hnRNA establish that the nuclear ribonucleoprotein particles are not formed artificially during isolation. In contrast to comparable material from mammalian cells (polydisperse, 40-25- S), Dictyostelium heterogeneous nuclear ribonucleoprotein particles sediment at only 55 S in sucrose gradients, possibly reflecting the smaller size of slime mold hnRNA relative to the large hnRNA found in higher eukaryotes. The RNA of the nuclear 55S ribonucleoprotein particles is shown to be hnRNA by virtue of its size (15S), content of polyadenylate sequences, and hybridization kinetics at DNA excess. The hnRNA-associated porteins are electrophoretically complex and have molecular weights between 20,000 and 150,000. In 0.35 M NaCl most of the proteins are released from the hnRNA. However, a single protein of 72,000-74,000 molecular weight remains bound, as indicated by its co-chromatography with the RNA on poly(U)-Sepharose and banding in Cs2SO4. The same protein is recovered when heterogeneous nuclear ribonucleoprotein is digested with T1 ribonuclease under conditions where the poly(A) is nuclease-resistant. The 73,000 molecular weight protein appears to be specifically bound to polyadenylate sequences in Dictyostelium hrRNA.


Induction of erythroid differentiation by dimethylsulfoxide in cells infected with Friend virus: relationship to the cell cycle. Cells infected with Friend virus can be induced to erythroid differentiation by culture with 2% dimethylsulfoxide. This study was designed to determine if dimethylsulfoxide causes the expression of erythroid differentiation by an effect on a particular phase of the cell division cycle. The infected cells were synchronized by exposure to 2 mM thymidine. It is shown that dimethylsulfoxide must be present during DNA synthesis (S-phase) and, possibly, shortly thereafter, to induce differentiation assayed by measuring hemoglobin synthesis. In order to achieve an effective intracellular incorporation of dimethylsulfoxide, cells must be exposed to the agent for at least 24-30 hr before the critical S phase. It is suggested that induction of erythroid differentiation in cells infected with Friend virus involves an effect of dimethylsulfoxide, or a metabolic product, that alters the program of transcription, during or immediately after DNA synthesis.


Cell-cell interactions: enhancement of glycosyl transferase ectoenzyme systems during Chlamydomonas gametic contact. Glycosyl transferase ectoenzyme systems that transfer galactose, glucose, N-acetylglucosamine, N-acetylneuraminic acid, mannose, and fucose have been detected on vegetative cells and gametes of Chlamydomonas moewusii. Gametes have higher levels of activity of the transferase ectoenzyme systems than morphologically identical vegetative cells, as determined by transfer of monosaccharide onto endogenous cell surface acceptors. When (plus) and (minus) gametes are mixed, there is a significant increase in the activity of transferase ectoenzyme systems. No enhancement in activity of transferase ectoenzyme systems occurs when (plus) and (minus) vegetative cells are mixed. Flagellar membrane vesicles obtained from (plus) and (minus) gametes show high activity of transferase ectoenzyme systems per mg of protein and also demonstrate enhanced activity upon mixing. Therefore, glycosyl transferases and acceptors seem to be located on the flagellar membrane and appear to have a function particularly related to gametic cells. The mechanism of cellular adhesion or recognition proposed by Roseman (1970, Chem. Phys. Lipids 5, 270-297), involving glycosyl transferases and acceptors, is strongly suggested by our data for the mating reaction in Chlamydomonas.


A general model for genetic recombination. A general model is proposed for genetic recombination. Its essential new feature is the hypothesis that recombination is initiated by a single-strand (or asymmetric) transfer, which may, after isomerization, become a two-strand (or symmetric) exchange. The likelihood of this transition from asymmetric to symmetric strand exchange determines certain characteristic features of recombination in any particular organism.


Distinct molecular structures of nuclear class I, II, and III DNA-dependent RNA polymerases. Class III RNA polymerases purified from the murine plasmacytoma MOPC 315 and from Xenopus laevis ovaries were compared. The subunit structures of the chromatographically distinct murine enzymes IIIA and IIIB were indistinguishable and were remarkably similar to that of the amphibian enzyme III. The plasmacytoma class III RNA polymerases were also compared with purified plasmacytoma RNA polymerases I and II. Sedimentation studies indicated that RNA polymerase III si significantly larger than RNA polymerase II, which is slightly larger than RNA polymerase I. Structural analyses showed that the molecular weights of the large subunits present in the class III enzymes (138,000 and 155,000) differ from those of the class II enzymes (140,000 and either 170,000, 205,000, or 240,000) and from those of the class I enzymes (117,000 and 195,000). Some low-molecular-weight subunits are also unique to each enzyme class. These results clearly distinguish the class I, II, and III enzymes on a structural basis. In addition, polypeptides of molecular weight 29,000 and 19,000 were found in all enzyme classes, a polypeptide of molecular weight 52,000 was found only in class I and III enzymes, and a polypeptide of molecular weight 41,000 was found only in class II and III enzymes. These findings are discussed in terms of the function and regulation of the RNA polymerases.


Short-lived messenger RNA in HeLa cells and its impace on the kinetics of accumulation of cytoplasmic polyadenylate. Accumulation of [3H]adenine in the acid-soluble pool and in nuclear and cytoplasmic poly(A) of HeLa cells shows that the nuclear poly(A) rises along a curve similar to that of the acid-soluble pool. By use of a [3H]guanosine pulse-chase experiment in adenine-grown cells, at least 35-50% of the pulse-labeled mRNA was found to have a half-life of about 1-2 hr. A mathematical model involving nuclear poly(A) synthesis and conservative transport to the cytoplasm has been derived from the new information about mRNA with a short half-life. This model predicts curves similar to those found for nuclear and cytoplasmic accumulation of poly(A). Thus, there is no necessity on kinetic grounds to invoke either nuclear turnover or cytoplasmic synthesis of poly(A).


Apocytochrome P-450: reconstitution of functional cytochrome with hemin in vitro. Synthesis of microsomal cytochrome P-450 in rat liver requires synthesis of apoprotein in rough endoplasmic reticulum and of heme in mitochondria. Dissociation of apoprotein and heme synthesis by concomitant treatment of rats with inducers of cytochrome P-450 (i.e., phenobarbital) and inhibitors of heme synthesis (i.e., cobalt) resulted in a relative excess of apocytochrome P-450. Under these circumstances, it was possible to reconstitute the holocytochrome by addition of hemin in vitro. The holocytochrome was detected spectrophotometrically by its CO-binding properties and functionally by its increased oxidative activity. Heme-mediated reconstitution was most efficient in cell fractions rich in mitochondria-rough endoplasmic reticulum complexes (640 times g fraction), suggesting that the structural association of these two organelles may represent a functional unit essential for the synthesis of holocytochrome P-450. These findings indicate that phenobarbital-mediated induction of apocytochrome P-450 is independent of heme synthesis. It is suggested that synthesis of the apocytochrome may be the primary and rate-limiting event in the formation of cytochrome P-450.


Reovirus messenger RNA contains a methylated, blocked 5'-terminal structure: m-7G(5')ppp(5')G-MpCp-. Reovirus mRNA synthesized in vitro by the virus-associated RNA polymerase in the presence of S-adenosylmethionine contains blocked, methylated 5'-termini with the structure, m-7G(5')ppp(5')G-MpCp. The functional significance and possible mechanism of formation of this novel 5'-5' terminal nucleotide linkage are discussed.


Enhancement of soybean RNA polymerase I by auxin. When etiolated soybean seedlings are treated with the synthetic auxin, 2,4-dichlorophenoxy-acetic acid, cells of the mature hypocotyl become swollen and proliferate abnormally. This abnormal growth induced by auxin coincides with a 5- to 8-fold increase in the alpha-amanitin-insensitive RNA polymerase associated with isolated chromatin or nuclei. The alpha-amanitin-sensitive RNA polymerase activity of the auxin-treated hypocotyl was similar to that of control tissue. The increase in RNA polymerase I activity of chromatin and nuclei was maintained after solubilization and fractionation on DEAE-cellulose. Auxin thus appears to enhance RNA synthetic activity (i.e., ribosomal RNA) in mature soybean tissue by altering RNA polymerase I directly rather than by altering RNA polymerase I directly rather than by altering the chromatin template.


Dimethyl adipimidate: a new antisickling agent. A new approach to the prevention of sickling in vitro by use of the bifunctional crosslinking reagent, dimethyl adipimidate, is described. Prior treatment of sickle erythrocytes with dimethyl adipimidate will inhibit sickling in completely deoxygenated erythrocytes. Treated erythrocytes do not demonstrate the potassium loss and viscosity increase that usually accompany sickling. The oxygen affinity of hemoglobin in these cells is increased independently from changes in the concentration of 2,3-diphosphoglycerate. The hemoglobin obtained from treated erythrocytes contains a high-molecular-weight component as well as additional positively charged components. The relative degree to which chemical modification and/or crosslinking is an essential part of the antisickling properties of the material is not known.


Sulfhydryl dependence in primary explant hematopoietic cells. Inhibition of growth in vitro with vitamin B12 compounds. Primary explants of P388, EL-4, and L1210 murine leukemia cells and of normal mouse bone marrow are shown to require sulfhydryl compounds for proliferation in vitro. Nine extablished cell lines show no stimulation by these compounds. Leukemia cells can lose the sulfhydryl dependence after various periods of adaptation to in vitro culture. Various sulfhydryl compounds have widely differing potencies in promoting in vitro proliferation of dependent cells. The effect appears to be specific for sulfhydryl groups in the reduced form. Vitamin B12 compounds inhibit the growth of sulfhydryl-requiring cells, apparently by catalyzing the oxidation of the sulfhydryl groups.


Studies on the primary structure of the influenza virus hemagglutinin. The amino-terminal sequence and composition of the subunits of the hemagglutinin (HA) of influenza virus has been determined. The hemagglutinin has been isolated by two techniques. (1) as the intact hemagglutinin after disruption of the virus in sodium dodecyl sulfate, giving 2 subunits of 58,000 daltons (HA1) and 26,000 daltons (HA2), and (2) after treatment of the virus with bromelain, giving 2 subunits of 58,000 daltons (BHA1) and 21,000 daltons (BHA2). In both preparations these subunits are linked by disulfide bonds. The aminoterminal sequences of HA1 and BHA1, and HA2 and BHA2 are the same. The composition of the 50 residue peptide associated with the membrane, which is removed from the C-terminus of HA2 by bromelain, is deduced and shown to be hydrophobic and contain 50% of the serine residues of HA2. The biosynthetic precursor of the hemagglutinin has been purified from the membranes of abortively infected chick fibroblasts and shown to have the same amino terminus as HA1. Thus the order of biosynthesis is NH2-HA1-HA2-COOH. The amino-terminal sequence of BHA2--at the cleavage site of the precursor--is shown to be a palindrome: NH2-Gly-Leu-Phe-Gly-Ala-Ile-Ala-Gly-Phe-Ile-. This sequence is conserved in representative viruses from each of the major pandemics. A region of homologous sequence is described between the hemagglutinins of influenza type A and B viruses.


A general method for the introduction of enzymes, by means of immunoglobulin-coated liposomes, into lysosomes of deficient cells. Phagocytes of the smooth dogfish (Mustelus canis) contain no endogenous peroxidase within their lysosomes and constitute models for cells genetically deficient in lysosomal enzymes such as myeloperoxidase. We have obtained uptake of over 50% of exogenous horseradish peroxidase, provided the enzyme is exhibited to cells after incorporation into liposomes coated with heat-aggregated (62 degrees, 10 min), isologous IgM. Trapping of horseradish peroxidase (EC 1.11.1.7) by liposomes was established by chromatographic resolution (Sephadex G-200; Sepharose 2B and 4B) of free enzyme from that associated with liposomes; liposome-associated horseradish peroxidase, together with trapped markers of the aqueous compartment (glucose, CrO4 equals), were excluded, and free enzyme and markers were retained. Enzyme and marker trapping was not electrostatic, varied with the molar ratio of charged membrane components, and was reversed by detergent lysis (Triton X-100) of liposomes. Uptake at 30 degrees of aggregated IgM-coated liposomes containing trapped horseradish peroxidase exceeded that of free enzyme of 100-fold, and was more efficient than uptake of horseradish peroxidase presented in uncoated liposomes or in liposomes coated with native IgM. After phagocytosis, peroxidase-rich liposomes were localized exclusively in lysosomes of the phagocytes by ultrastructural histochemistry; the enzyme displayed over 50% latency to osmotic lysis. This method may prove to be of general use in the provision of exogenous enzymes to phagocytic cells genetically deficient in lysosomal hydrolases.


Effects of ionizing radiation on DNA replication in cultured mammalian cells.


Serum immunoglobulin levels in humans exposed to therapeutic total-body gamma irradiation.


Acute renal failure in McArdle's disease and myoglobinuric states. Reversible acute oliguric renal failure associated with skeletal muscle abnormalities due to either McArdle's disease or myoglobinuria developed in two patients. Renal angiographic and hemodynamic data revealed a preferential diffuse reduction in cortical perfusion. Arteriography showed absence of a cortical nephrogram and attenuation of the distal interlobar and arcuate arteries. Contrast medium was delayed in passage through the edematous kidney. These changes are distinct from those of chronic renal failure due to parenchymal disease. The renal arteriogram can be a useful adjunct in the differential diagnosis of acute renal failure of obscure origin.


Erythroleukemia following total-body irradiation for advanced lymphocytic lymphoma. A patient with advanced lymphocytic lymphoma received treatment with total-body irradiation. Two years later acute erythroleukemia developed which proved fatal. Previous experience with total-body irradiation is considered and the relationship between radiation exposure and leukemia discussed.


Rehabilitation needs of the cancer patient.


Heritable cell cycle disturbances and late recovery in x-irradiated murine lymphoma L5178Y-S cell populations in vitro. 1. Ionizing radiation can induce in mammalian cells, besides the lethal effects, also heritable damages which retard cell cycle traverse for considerable humber of cell generationsl 2. Radiation-induced heritable lesions in murine leukaemic lymphoblasts L5178Y-S affect progesssion of the cells through the G2 phase of the cell cycle. 3. Late recovery of proliferative activity which must be connected with elimination of the G2 block is a common phenomenon in the heritably damaged L5178Y-S sublines derived from single cells. 4. A possibility should be taken into consideration of employing the cells heritably damaged by radiation as convenient models for studies on some disturbances which accompany ageing of the mammalian cells. 5. It seems that results of studies on both the cells heritably damaged by radiation and the ageing cells could be useful for evaluation of possibilities of prevention, control or elimination of the heritable cell cycle disturbances.


Cytochemical and cytogenetic findings in five human leukocyte long-term cultures (LAHL) of different origin. Five human leukocyte long-term suspension cultures were investigated by means of cytochemical and cytogenetic methods. A striking resemblance in the morphology of these cells originating either from peripheral blood or from spleen of patients with or without hematological disorders was found. Lymphocytic origin of all five cultures is suspected. In the three cultures a diploid karyotype was found with some aberrations. In one culture, derived from the spleen of a patient with panmyelopathy the mosaic 45 XX C -/46 XX was detected. Anomalies of C group chromosomes were the most consistent type of chromosome aberrations in two lines. Both were EBV positive.


Proliferation and morphology of ascitic cells as a function of age in cell culture. Ascitic cells in the logarithmic growth phase increase the accumulation of glycogen particles in the course of explantation into suspension culture, probably due to the increasing arrest of glycogenolytic enzymes. At this age, a part of the cells are capable of restitution by exopinocytosis of the glycogen-containing vacuoles ia formation of cytoplasmic buds. Older cells, taken from the plateau-phase, pass atypical differentiation and ageing, are less capable of hindering the abnormal accumulation of glycogen and the hypervacuolisation. As a consequence, the cells finally degenerate and die.


Ribonucleases in mouse ascitic tumor cells during ageing in vivo and in vitro. Ribonuclease activities have been determined in cell extracts of mouse L5178Y lymphoma grown in vivo and in vitro. From the obtained results it follows that the level of studied enzymes changes in both systems during ageing of the cells. Moreover, when lymphoma cells are cultured in vitro a marked decrease in specific activity of alkaline ribonuclease II is observed.


Ultrastructure of the sinus wall of murine bone marrow in myelogenous leukemia. The ultrastructure of bone marrow of RF mice having an acute myelogenous leukemia induced by inoculation with leukemic cells was investigated. In several respects sinuses of leukemic marrow are similar to normal marrow. Sinuses are present in numbers approximating that of the normal; the lining cells of the sinus wall have organelles similar in distribution and number to those of normal lining cells; the sinus wall is continuous, having openings only in conjunction with blood cells that are migrating through it (migration pores); migration pores occur within and not between lining cells. Abnormalities observed in leukemic marrow are the occurrence of virus-like particles in leukemic cells, the presence of numerous particles 300 to 500 A in diameter in the extracellular space, reduction in the number of adventitial cells of the sinus wall and an increase in the thickness and distribution of extracellular material located near the basal surface of lining cells.


Spinal cord vascularization by intact omentum.


Excess leukemia in cohorts of children born following influenza epidemics. Two series of data from the California State Department of Health and one from Children's Hospital of Los Angeles were analyzed to determine whether an association exists between influenza epidemics and incidence of leukemia in children born following such outbreaks. Of leukemic children born in areas for which information on past influenza activity was available, the population-based Alameda County Cancer Registry recorded 89 cases during 1960-1969, the California Tumor Registry recorded 653 cases during 1950-1970, and Children's Hospital recorded 575 cases during 1957-1972. Flu epidemics were identified and flu cohorts constructed such that leukemic children who could have been in utero during a flu epidemic constituted a flu cohort. Based on the total number of leukemia cases reported and the proportion of at-risk weeks contributed by the flu cohort, expected numbers of leukemia cases from the flu cohort were computed for each age. In each series, there was an excess of leukemia cases in the flu cohort, contributed primarily by the 0-4 age group. Trimester analysis indicated that the greatest excess occurred in children who were in the first trimester of gestation during a flu epidemic. Incidence data from the Cancer Incidence System of the San Francisco Bay Area Resource for Cancer Epidemiology and the Third National Cancer Survey show a relative risk of 3.4 for this group. Due to sources of misclassification in this study, such as analysis of flu cohorts rather than individuals whose mothers actually had influenza during pregnancy, the results tend to be diluted. If influenza is a causative factor, the actual increase in leukemia risk is likely to be much greater than this analysis indicates.


Presence of neurophysin proteins in tumors associated with the syndrome of inappropriate ADH secretion.


Platelet function in patients with high platelet counts. Platelet function tests were done to ascertain whether they might have discriminatory significance in the differentiation of a myeloproliferative disorder from secondary thrombocytosis in a patient with an elevated platelet count. Amongst 14 subjects with polycythaemia vera and essential thrombocythaemia, significant abnormalities of platelet aggregation were the rule, while defective aggregation was unusual in 16 subjects with secondary thrombocytosis. Measurements of the bleeding time and of platelet factor 3 activity were of some value, but significant overlap was noted. Platelet function in four of five subjects with chronic myeloid leukaemia was essentially normal.


Neurophysins I and II from the bovine posterior pituitary lobe and neurophysin-like proteins from bovine pineal gland.


Presence of immunoreactive neurophysin-like material in human target organs and pineal gland: physiological meaning.


Some properties of neurophysins isolated from bovine neurosecretory granules. Our experiments with the neurophysin-related proteins from bovine NSG have demonstrated that these species differ in several important respects from the materials conventionally prepared. (1) In structural terms, the NSG proteins are essentially identical with the conventional neurophysins in amino acid composition and closely similar in immunoreactivity; however, the presence of carbodydrate and lipid moieties in the NSG material, no matter how they are attached, constitutes a structural difference apparently sufficient to cause considerable changes in properties. (2) The affinities for the neurohypophyseal hormones of the NSG proteins are very much higher than those of the "conventional" neurophysins and, moreover, the binding properties of the NSG material are much more stable with time under the conditions of the binding experiments. (3) The low binding capacities of the NSG materials, even when they are purified to apparent molecular homogeneity, indicate a functional heterogeneity perhaps related to supramolecular structure. (4) The conversion of the NSG proteins by acid or alkali treatment to materials resembling the "conventional" neurophysins in their binding properties suggests that the latter may be isolation artifacts. Although we cannot as yet consistently explain the properties of our neurophysins from NSG, we offer the hypothesis that the low binding capacity, as also the Hill coefficient greater than 1 (cf. Reference 25) are indicative of molecular aggregation, perhaps mediated or facilitated by the nonprotein components. It is conceivable that such aggregation, proceeding in the more "natural" environment of the NSG in a more precisely organized manner, might constitute the truly "native," fully functional state of the neurophysins. In this context it is of interest to record our preliminary observations, which suggest the presence of a protein of 10,000 mol. wt. in the NSG membrane fraction (SDS gel) as well as electron-microscopic indications30 of a highly organized ("crystalline") structure within these membranes. Although, therefore, the materials we have described may not merit the description of "native" neurophysins, we believe that they are certainly closer to the native state than the proteins conventionally isolated; and we would suggest that any discussion of the biological role of the neurophysins based on the properties of the conventional preparations may be at best speculative, and at worst misleading.


Soluble acidic lipoproteins in neurosecretory granules: relation to neurophysins.


Radioimmunoassay of neurophysin proteins: utilization of specific neurophysin assays to demonstrate independent secretion of different neurophysins in vivo.


Release and clearance of neurophysins and posterior pituitary hormones.


Radioimmunoassay of neurophysin I and II in human plasma.


Cytologic changes in Erlich ascites tumor treated with antiblastic drugs and hyperbaric oxygen.


The radioimmunoassay of human neurophysins: contribution to the understanding of the physiopathology of neurohypophyseal function.


Observations on the lipolytic and melanotropic properties of neurophysin proteins. Previous work indicated that brain contains 3 types of lipolytic-melanotropic peptide: (1) in adenohypophysis: ACTH, alpha-MSH, beta-MSH, peptide I, peptide L', beta-lipotropin and gamma-lipotropin; (2) in neurohypophysis: peptide 7D6, also termed neurophysin I, peptide II or Wuu-Saffran peptide; (3) in extrahypophyseal regions: peptide IIF. Bovine and human neurophysin I prepared by R. Walter has now been found devoid of lipolytic and melanotropic activities. Porcine and bovine peptide 7D6, closely similar or identical to bovine neurophysin I in electrophoretic mobility and amino acid composition, were therefore reexamined to determine whether their lipolytic-melanotropic property resided in a contaminating factor. When peptide 7D6 was analyzed in 100 transfer counter current distribution (1 butanol/0.1M NH4 HCO3), the neurophysin was recovered in tubes 1-9 (7D6-alpha) representing 95% of 7D6. 7D6-alpha was inactive in lipolytic and melanotropic assays. The biologic activities of 7D6 were recovered instead in tubes 50-70 (labeled 7D6-beta), representing 5% of 7D6. 7D6-beta proved to be a peptide with MW 1000-3000, closely similar to peptide IIF in amino acid composition, MW, and Rf values in 4 systems of paper chromatography.


Metabolic activities of human neurophysins.


Biologic activity of neurophysin: natriuresis.


Neurophysin binding and naturiuretic peptides from the posterior pituitary.


Quantification of rat neurophysins by polyacrylamide gel electrophoresis (PAGE): application to the rat with hereditary hypothalamic diabetes insipidus.


Guinea pig neurophysin: isolation, developmental aspects, biosynthesis in organ culture.


Recent advances in the purification of neurophysin proteins.


Slab gradient gel electrophoresis in the analysis of neurophysins.


Nondipolar contributions to 13C relaxation in molecules.


On the mechanism of binding of neurohypophyseal hormones and analogs to neurophysins.


Conformational effects associated with the interaction of polypeptide ligands with neurophysins.


Heterogeneous binding sites in neurophysin-like macromolecules: some theoretical and computational considerations.


Primary structure and evolution of neurophysins.


Structural studies of bovine neurophysin-I.


Environmental health hazards from high-powered, infrared, laser devices. The potential health hazards associated with high-power laser systems are not limited to the direct beam. In addition to the obvious hazards of direct beam exposure of personnel, environmental problems may arise from electrically-energized equipment, excessive noise from the laser itself, and from hazardous fumes, gases, and vapors originating from components of the laser or from the target material.


Distributions of symmetric and asymmetric patterns of caries attack in human permanent mandibular incisor teeth: genetic implications.


The neurophysin proteins: historical aspects.


Action potentials from a model tooth.

Action potentials from a model tooth.


Progress in the treatment of osteogenic sarcoma.


Distribution of PZ-peptidase and glycylprolyl beta-naphthylamidase activities in oral tissues.


Histological differences in the epithelium of denture-bearing and non-denture-bearing human palatal mucosa.


Experimental determination of the rigidity modulus, Poisson's ratio and elastic limit in shear of human dentine.


Fatty acid composition of carious molar enamel and dentine from rats deficient in essential fatty acids.


Observations on tooth replacement in piranhas (Characidae).


Amino acid composition, distribution and origin of "tuft" protein in human and bovine dental enamel.


Interaction between tooth germs and the adjacent dental lamina in the mouse.


The unit-cell dimensions of human enamel apatite: effect of chloride incorporation.


Blood flow in the dental pulp in dogs measured by local H2 gas desaturation technique.


Biological activities in human labial and palatine secretions.


Metals in dentinal tubules beneath amalgam fillings in human teeth.


Sialic acid and hexosamine content in the sublingual glands from rats fed a vitamin A deficient diet.


In vitro production of sulphated mucosubstances by the labial and palatine glands of the monkey Macaca irus.


The ultrastructure of bacterial plaque attached to the gingiva of man.


The effects of cyclophosphamide on odontogenesis in the rat.


Development of a gomphosis by tooth germ implants in the parietal bone of the mouse.


Dental floss for implantation and sampling of Streptococcus mutans from approximal surfaces of human teeth.


Effects of dietary restriction on the composition of lipids in rat teeth.


An autoradiographic study of the effect of a range of fluoride doses on the utilization of (3-H)-orotate by ameloblasts in the rat.


The pattern of eruption of some human teeth.


Current status of chemotherapy of solid tumors.


Coarctation of the aorta, both subclavian arteries originating from the distal segment and absent left carotid artery: report of a case.


Effect of feeding different levels of corn oil on the composition of submandibular salivary gland fatty acids in rats.


Response rate and reasons for non-response in an epidemiological study - The Puerto Rico heart health program.


Editorial: Attitudes.

Editorial: Attitudes.


Letter: An untoward incident.

Letter: An untoward incident.


Letter: Area dental advisory committees.


Letter: 'Circulating levels of lignocaine after perio-oral injections'.


Letter: Levels of fluoride.

Letter: Levels of fluoride.


Perception of malocclusion.

Perception of malocclusion.


Cancer incidence in relation to fluoride level in water supplies.


Oral hygiene in mentally handicapped children. A pilot study of the use of chlorhexidine gel.


Joint Committee for Higher Training in Dentistry.


Radiological protection in dentistry--the new service after 1 year's operation.


Entry to dental schools with 'A' level in mathematics rather than biology.


Letter: The use of ancillaries.

Letter: The use of ancillaries.


Editorial: The I.A.D.R. in London.

Editorial: The I.A.D.R. in London.


Dibromomannitol in the treatment of chronic granulocytic leukemia: a prospective randomized comparison with busulfan. Dibromomannitol (DBM) is a new agent for the treatment of chronic granulocytic leukemia. A propsective evaluation of the drug was undertaken in a randomized comparison with busulfan. Forty previously untreated, Philadelphia chromosome-positive cases were treated, with 20 patients in each treatment group. The protocol provided for continuous maintenance therapy after remission induction, with a crossover to the opposite drug in patients who became refractory to the primary agent but are without evidence of blastic tranformation. There were 14 remissions in the DBM group and 15 in those treated with busulfan. The rate of decrease of the elevated leukocyte count was more rapid with DBM, but prolonged disease control off treatment occurred in only three of 14 cases as opposed to nine of fifteen busulfan-treated patients who required a median delay of 12 mo before maintenance could be initiated. Hypoplasia occurred in one DBM patient and two busulfan cases. Following recovery, crossover to the opposite drug in two cases again resulted in hypopllasia. Increased skin pigmentation, amenorrhea, pulmonary fibrosis, and cytologic dysplasia, commonly associated with busulfan adminstration, were also noted with DBM. The median duration of disease control with busulfan was 34 mo and 26 mo with DBM. There was no signigicant difference in the incidence of blastic transformation, and median survival for both groups was 44 mo. DBM appears to be as effective as busulfan in the treatment of the chronic phase of CGL but with a more predictable myelosuppressive action. The principal advantage of busulfan over DBM is the fact that more than half the busulfan-treated patients experienced prolonged disease control off treatment.


Extraction techniques for low-seated dentistry.


Report of the Representative Board to the Annual General Meeting of Members, 1975.


Measurement of vitamin B12-binding proteins of plasma. II. Interpretation of patterns in disease. The technique described in the preceding paper was applied to 12 abnormal sera selected for their increase in one or more B12-binding proteins. Even in the presence of large amounts of R-type binder, the ammonium sulfate technique gave a reliable separation of R binding proteins from TC II. Measurement of the TC II in abnormal sera gave results identical to those obtained by the more standard gel filtration. The R binders of four subjects with myeloproliferative disease were further separated into alpha2-R and alpha1-R. The pattern  of B12 binding of polycythemia vera (PV) was an exaggeration of the normal pattern. Binding to alpha2-R was three to four times that to alpha1-R, although the total amounts bound to both were increased. In chronic myelogenous leukemia (CML), both alpha2-R and alpha1-R were also increased, but in contrast to binding in normal sera, alpha1-R predominated.  In order to interpret the findings, either whole serum R or alpha1-R and alpha2-R from patients with myeloproliferative disease were subject to isoelectric focusing. Alpha2-R consisted pricipally of components isoelectric at pH 2.9, 3.0, and 3.1. These components were present in only minor amounts in normal serum and were somewhat increased in the serum of PV. These components were very much increased in the serum of CML and predominated. Alpha2-R consisted of those components isoelectric at pH 3.4,3.6, and 4.0. These components predominated in the unsaturated binding capacity of normal sera and that of PV. It was concluded that the division of plasma R binders into alpha1-R and alpha1-R by the technique described provided information useful in the study of myeloproliferative diseases.


Artificial liver support in fulminant hepatic failure.


De novo appearance of the ph-1 chromosome in a previously monosomic bone marrow (45,XX,-6): conversion of a myeloproliferative disorder to acute myelogenous leukemia. Bone marrow examination of a patient with a myeloproliferative disorder revealed monosomy for chromosome No. 6 (45,XX,-6). Two months later, during blastic crisis, reinvestigation of the bone marrow showed the presence of the Ph-1 chromosome in the previously aneuploid cell line (45,XX,-6,-22,+Ph-1). This case differs from those previously published in that the Ph-1 chromosome appeared de novo during the development of frank acute myelogenous leukemia.


Isoleucine metabolism by leukemic and normal human leukocytes in relation to cell maturity and type. The metabolism of an essential amino acid, isoleucine, by human leukemic and gradient-separated normal human leukocytes of various types and maturity was studied. Blood leukocytes were isolated and incubated with (U-14C) isoleucine. Separation of metabolic intermediates was accomplished by sequential extraction. The rate of isoleucine incorporation into protein by immature cells from untreated patients with acute leukemia (15.9 plus or minus 2.4 nmoles/hr per 10-8 leukocytes) was considerably higher than the rates of incorporation by mature neutrophils (3.2 plus or minus 0.5 nmoles/hr per 10-8 leukocytes), lymphocytes (7.7 plus or minus 1.2 nmoles/hr per 10-8 leukocytes), and eosinophils (6.2 plus or minus 1.3 nmoles/hr per 10-8 leukocytes). Those cell preparations with more blast cells had higher rates of protein synthesis. In addition, those cells with greater thymidine incorporation had higher rates of protein synthesis. The leukocytes both oxidized isoleucine and incorporated it into cell isoleucine and incorporated it into cell lipid. The rates of these metabolic processes were characteristic for various types and maturity of leukocytes. This study demonstrates a relationship of rate of protein synthesis to leukocyte immaturity. This relationship is maintained in neoplastic leukocytes. It suggests that the requirement of the mitotic process for newly synthesized protein is greater than that for the elaboration of the protein products of the mature leukocyte.


The clinical value of endoscopic retrograde cholangiopancreatography.


Primary granulocytic sarcoma of the small bowel. A young man developed obstruction of the small bowel due to a neoplastic process, which in retrospect proved to be a primary granulocytic sarcoma, preceding acute granulocytic leukemia for more than 3 years. The histologic, histochemical and ultrastructural findings are presented, together with a review of the literature on granulocytic sarcomas, particularly those presenting as aleukemic forms. It is suggested that these forms may not be so rare and that careful search, using currently available methods, will be rewarding.


Lymphocyte transformation in leukemic serum. Cultures of normal lymphocytes were induced to transform by pokeweed mitogen (PWM). Inhibition of transformation was observed when these cultures contained sera isolated from children with acute lymphoblastic leukemia (ALL). The inhibition of transformation of normal lymphocytes was best demonstrated when the concentration of the leukemic serum in the culture medium was relatively high (60 percent); however, the inhibition was also observed with a more standard serum concentration (20 percent). Not all leukemic sera were inhibitory. Pretreatment sera from newly diagnosed patients with leukocyte counts greater than 50,000/mm3 were significantly inhibitory. Pretreatment sera from newly diagnosed patients with leukocyte counts less than 50,000/mm3, and sera from patients in remission or relapse had no significant effect. The inhibition observed with the sera of the high leukocyte count group was not believed to be related to cytotoxicity. The significance of this inhibitor in relation to clinical prognosis needs to be investigated.


Occurrence of hepatitis and hepatitis B surface antigen in adult patients with acute leukemia. Fifty-eight adult patients with acute leukemia were screened at the onset of the disease for hepatitis B antigen (HBSAg) in the serum, and during the course of the disease for the development of hepatitis B. One patient had a positive test for HBSAg by the radioimmunoassay technique only at the time leukemia was diagnosed; this patient had received transfusions some years before. In six patients icteric hepatitis B developed; five recovered completely and one died of leukemia during the course of hepatitis. All patients in whom hepatitis developed had received transfusions as a part of supportive therapy for leukemia. The hepatitis risk for patients who received transfusions of blood found to be negative for HBSAg by counterimmunoelectrophoresis was 0.26 percent per unit of blood administered.


Painful lytic bone lesion in an adult with chronic myelogenous leukemia. The occurrence of blast cell granulocytic tumors (chloromas, myeloblastomas) associated with chronic myelogenous leukemia has been well documented. However, the production of lytic lesions by nonmyeloblastomatous hematopoietic cell forms in chronic myelogenous leukemia has been described only once previously. The pain associated with osteolysis in this particular patient preceded roentgenographic appearance of lytic lesion and diagnosis of chronic myelogenous leukemia. Biopsy of lytic lesion demonstrated infiltration with cell forms nearly identical with those of simultaneously performed bone marrow aspiration.


Alteration of methotrexate uptake in human leukemia cells by other agents. The uptake of methotrexate (MTX) and the effect of drugs known to either inhibit or enhance MTX transport in L1210 murine leukemia were studied in man using blast cells from patients with acute myelogenous leukemia in vitro. MTX uptake was found to proceed slowly, requiring at least 160 min for cells to reach a "steady state" when extracellular MTX concentrations were 1 muM. Efflux of MTX from preloaded cells required 80 to 120 min and the nonexchangeable or tightly bound fraction was 40% of the total intracellular drug. Utilizing doses that are estimates of achievable peak blood levels following single i.v. injection, cephalothin (21 mug/ml) and hydrocortisone (20 mug/ml) inhibited net MTX accumulation by 20 and 28%, respectively. Vincristine sulfate at 8.3 and 0.083 mug/ml enhanced MTX uptake by 54 and 33%, respectively, by inhibiting MTX efflux, thus increasing the level of intracellular drug in excess of the tightly bound fraction. The potential clinical implications of using MTX in combination with the aforementioned drugs for cancer chemotherapy are discussed.


N-trifluoroacetyladriamycin-14-valerate, an analog with greater experimental antitumor activity and less toxicity than adriamycin. N-Trifluoroacetyladriamycin-14-valerate (AD 32), an analog of adriamycin, exhibits significantly greater antitumor activity than does adriamycin or daunorubicin in two experimental mouse tumor systems under similar assay conditions (C57BL X DBA/2 F1 male mice, agents administered i.p. each day for Days 1 to 4). Against the P388 leukemia at optimal dosages, AD 32 gave a +429% increase in median life-span with 3 of 5 60-day survivors compared to +132% for adriamycin (no 30-day survivors). In the L1210 leukemia system, AD 32 at several dosages consistently and reproducibly effected an increase in lifespan in excess of 445%, with a high percentage of 60+-day survivors compared to adriamycin (+42 to +54% ILS; no 30-day survivors). The reduced toxicity of AD 32 was evidenced by its optimal dose range, which is significantly greater than the lethal dose for 100% of mice of adriamycin, and by its lack of delayed toxicity. In vitro, AD 32 was somewhat less effective than was adriamycin in inhibiting the growth of CCRF-CEM cells; enzymatic conversion of AD 32 by cell-free culture medium was not observed. The unique growth-inhibitory properties of this analog indicate that the therapeutic effectiveness of the anthracycline antitumor antibiotics can be retained or enhanced by substitution on the glycosidic amino group.


Leukocyte function in children with malignancies. Blood was obtained on 414 occasions from 106 children with acute lymphocytic leukemia (ALL) or solid tumors. Resting and stimulated hexose monophosphate shunt (HMPS) activity and unstimulated and stimulated nitroblue tetrazolium (NBT) dye reduction were assessed on each sample. The values obtained were compared to similar determinations made on blood obtained from 178 healthy children. Resting HMPS activity of all patients with malignant diseases was significantly (p smaller than 0.01) greater, and ability to stimulate HMPSP activity significantly (p smaller than 0.01) less than that noted in healthy control patients. Unstimulated NBT dye reduction of leukocytes obtained from patients with malignant disorders was significantly (p smaller than 0.01) less than that observed in healthy control children. No significant differences were noted in HMPS activity or NBT dye reduction in patients with ALL, rhabdomyosarcoma, or other solid tumors who had bacterial infection when compared to uninfected patients, or when patients were categorized according to the type of chemotherapy provided. HMPS activity and NBT dye reduction of patients with ALL prior to treatment, in remission, and during episodes of relapse did not differ from each other. Thus, a functional impairment in leukocyte function was noted in patients with ALL even when their peripheral blood and bone marrow cells exhibited normal morphology.


Habilitation of severe craniofacial anomalies--the challenge of new surgical procedures: an NIDR workshop. Three NIDR-sponsored workshops were conducted with the goal of identifying research needs in treatment and basic sciences relating to a group of severe craniofacial anomalies that are now correctable by new radical surgical procedures. Experts in the fields of developmental biology, neurosurgery and reconstructive craniofacial surgery discussed areas of investigation dealing with etiology, prevention and treatment that are most likely to result in clincally-useful information. In addition the establishment of craniofacial anomalies centers for data collection, treatment and research was examined.


A clinical investigation of the efficacy of primary nasopalatal pharyngoplasty.


Sociological aspects of cleft palate adults. III. Vocational and economic aspects. Vocational and economic aspects of social functioning were evaluated for 196 adult cleft subjects, their 190 siblings and 209 random controls. Results indicated that cleft adults functioned within normal limits with regard to employment. However, levels of income were substantively lower than control groups. Cleft subjects compare favorably with their siblings and random controls in  occupational mobility over the levels attained by their fathers. It would appear that cleft subjects experience some limitation in their ability to secure vocational and economic rewards from society.


The effects of clefting on crown-root length, eruption, height and weight in twins discordant for cleft of lip and/or palate. Within-twin differences for crown-root length and eruption of the mandibular buccal teeth were examined for 14 DZ and 14 MZ like-sexed twins discordant for cleft of lip and/or palate. The differences were found to be greater between DZ twins than between MZ and seldom statistically significant. Relatively large variances associated with the differences are attributed to widely varying levels of postnatal care for this sample. The within-twin differences were also analyzed according to type of cleft. Cleft of lip only was found to have a lesser effect on root-crown length and percent eruption differenes than cleft or palate (or cleft of lip and palate) although again not a statistically significant difference. Height and weight were found to follow a similar pattern including large variances associated with the within-twin differences. It is therefore concluded that a dysmorphogenic effect of clefting on crown-root length, eruption, height and weight cannot be demonstrated in this sample because of large associated variances due in turn to varying levels of post-natal health care and multiple other aspects of the syndrome.


Human palatal development. In vitro.

Human palatal development. In vitro.


A tomographic technique of assessing lateral pharyngeal wall displacement. Various methods of specifying lateral pharyngeal wall configuration during speech and other activities are reviewed. Basic tomographic principles also are reviewed and a new tomographic technique of measuring mesial displacement of the pharyngeal walls is presented. An important advantage of the technique described in this report is that it enables one to measure the degree and level of mesial displacement of the lateral pharyngeal walls in relation to the soft palate, tongue, and other structures observable on lateral-view radiographs.


Articulation patterns and speech intelligibility of 54 Vietnamese children with unoperated oral clefts: clinical observations and impressions. Evaluations of the articulation patterns and speech intelligibility of 54 Vietnamese children with unrepaired oral clefts indicate a relationship between the type of oral cleft and the proficiency of speech skills attained. The results of the study suggest that consideration of the type of oral cleft and the specific kinds of articulation errors exhibited by the patient may be of value in planning the surgical habilitation of older children and adults with unrepaired clefts of the lip and palate.


Cleft palates and middle ear effusions in babies.


Delayed pharyngeal flap success: report of a case.


Pulmonary fungal infection complicating treated malignant disease. Secondary pulmonary fungal infection in patients being treated for malignant disease may be difficult to diagnose. Nine patients are described, illustrating some of the possible radiological appearances. There was pathological support for the diagnosis in seven of these patients. A plea is made for a higher level of suspicion in patients with the predisposing factors who also develop pulmonary complications so that suitable treatment may be given, even though sputum examination is negative.


Pharmacokinetics of guanazole in patients with acute myelocytic leukemia. Levels of guanazole (GZ) in plasma and packed cells were determined after a single tracer dose of 14C-guanazole or during a 5-day continuous intravenous therapeutic infusion of unlabeled drug to 5 patients with acute myelocytic leukemia (AML). The levels of unlabeled drug were determined colorimetrically. GZ infected as a tracer dose was rapidly distributed in an apparent volume of 0.61 l/kg, which is somewhat less than that of total body water, and the drug appeared to be eliminated essentially unchanged by glomerular filtration. The mean apparent volume of distribution increased by about 15% during infusion. An increase of 60% was also noted in the half-life (t1/2) values, with a concimitant decrease in the mean value of renal clearance rate by 40%, except in 1 case. The study demonstrates that monitoring levels of guanazole is possible during infusion therapy and indicates that the data could be used to evaluate pharmacokinetic parameters predicting the time-course of such levels in patients.


Everything you always wanted to know about tax audits.


A patient's eye view of you.

A patient's eye view of you.


Does that annual report add up?

Does that annual report add up?


The silent partner in your office.

The silent partner in your office.


Human leukemic cells: characteristics of modified methylated minor bases of low molecular weight ribonucleic acids.


Coexisting with your dental laboratory.

Coexisting with your dental laboratory.


Makings of malpractice: The case of the hot pursuit.


Oil and gas: things the broker never told you.


Unsafe at any speed?

Unsafe at any speed?


How to survive through '75...and beyond!


For the trip of your life: try LSD.

For the trip of your life: try LSD.


Should you admit you're human?

Should you admit you're human?


Caution: dentistry can be hazardous to your health.


Stress without distress.

Stress without distress.


How to duplicate radiographs.

How to duplicate radiographs.


Modified technic aids accuracy in processing complete dentures.


The dental significance of corticosteroids, antihypersensitive drugs and anticoagulants.


Technic promises 'almost instant' pain relief.


'We still see tetracycline-stained teeth: physicians must be told'.


To 'clinch' case presentation, reinforce it in writing.


The supplier: Dentistry's 'natural ally'.


Improving the palatal seal in complete upper dentures.


Dentistry's obligation--and reward: 'service for the human welfare'.


Bungalow turns into 'gingerbread office'.


The diagnostic quagmire of muscle diseases in adulthood.


Some endocrine influences on hypothalamic hyperphagia.


Benign migratory glossitis.

Benign migratory glossitis.


A biometrical analysis of a mating characteristic in Drosophilia. A model is described for the biometrical analysis of interaction behavioural characteristics. The model is illustrated by analysis of the mating speed of Drosophila pseudoobscura derived from crosses of fast and of slow mating strains generated through artificial selection.


Population cytology of the genus Phaulacridium. Ten of the 27 populations of Phaulacridium marginale collected from South Island, New Zealand, during the 1973 meiotic season were polymorphic for extra heterochromatin. This was present either as B chromosomes or as super-numerary segments on the shortest autosomes. In some populations both polymorphisms were present simultaneously, sometimes at high frequencies. Three different types of B chromosome were seen; large telocentric, small telocentric and small metacentric isochromosomes though only one type was seen in any one population. Segments on the telocentric S9 and S10 chromosomes were located distally. On the S11 chromosome, however, the extra segment was present as a short arm, thus making the chromosome submetacentric. This latter situation is similar to that in the related species Ph vittatum. The frequency of B's in the OM population appeared to be stable over years and there was no indication of any meiotic "drive" or "drag" in the males. The frequency of occurrence of B chromosomes in a population correlated negatively with annual rainfall (low B frequencies in regions of high rainfall). Neither type of extra heterochromatin had any significant effect on either mean cell chiasma frequency or on log variance of this metric. Possible synergism between B's and segments is discussed from the preliminary analysis of the OM population. The probable origins and age of the polymorphisms are discussed in detail.


A new hypothesis for the origin of the parthogenetic grasshopper Moraba virgo. It is proposed that Moraba virgo, the only all-female grasshopper, originated by hybridisation between two extant species P169 and P196. Such an origin accounts for M. virgo's peculiar karyotype and pattern of late replication. The model is predictive and experiments are suggested to test it.


Testing models for variation in intelligence. A biometrical-genetical model for human variation adequately predicts observed correlations for measured intelligence. The estimation procedure is outlined.


Linkage disequilibrium causing selection at a neutral locus in pooled Tribolium populations. The role of linkage disequilibrium with respect to the changes in allele frequencies at a marker locus in newly started polymorphic populations is demonstrated using the marker locus black in Tribolium. The experiments, jointly taken, indicate that the black locus is selectively neutral, or nearly so, under the current experimental conditions. A number of possible mechanisms for selection at the neutral marker locus, i.e. a single linked or non-linked locus and a number of linked and/or non-linked loci through which selection acts, are discussed. On the basis of the experiments some of these models can be excluded, leaving three models for further evaluation: (A) a single linked fitness locus, (B) a number of linked fitness loci and (C) a number of both linked and non-linked fitness loci. The first of these models allows estimation of parameters (recombination  fraction and selection coefficients). Models B and C are described in terms of heterozygosity of chromosome pairs. It is argued that in view of the history of a laboratory mutant stock, model C fits best to the experimental results.


The relation of phenotype to habitat in an introduced colony of Cepaea nemoralis. The introduced colony of Cepaea nemoralis at Lynchburg, Virginia, contains only yellow shells. The population respond to the characteristics of the environment by adjusting the frequencies of the banding morphs and by regulating the amount of fusion of adjacent bands. In this respect they fulfill a prediction based on the observations of Clarke (1960) on British colonies of Cepaea hortensis.


Extrachromosomal factors affecting mating reactions in Schizophyllum commune. Extrachromosomal factors modifying mating reactions in Schizophyllum commune were found. The P factor appeared spontaneously, while the F factor appeared following nitrosoguanidine treatment. When a strain carrying P was mated with wild-type strains, it invariably developed pseudoclamps (usually typical of common-B heterokaryons), while there developed on the side of the wild-type strain the dikaryon or heterokaryon expected from the genotypes involved. In a cross Ax Bx P times Ay By, fruiting bodies from the side of the wild type gave rise only to wild-type segregants with mating types as expected from their genotypes. A selfed fruiting body from the side of the P strain gave rise to progeny which did carry the P factor, but its expression was modified. It had inconsistent and symmetrical effects in A not equal to B not equal to and A not equal to B equals matings, but the original type of asymmetrical reaction in A equals B not equal to matings. In the next generation the effect of P was weak and symmetrical. Strains carrying F factor were flat (morphology typical of mutation of the B factor) and were compatible with strains with which they should be incompatible according to the genotypes, e.g. Ax Bx F times Ay Bx gave a dikaryon. The factor showed non-Mendelian segregation and was extremely unstable.


[Editorial: What you don't add can't hurt you].


Letter: Ontario's Royal College of Dental Surgeons censured.


Viewing the task force on quality evaluation.


How should the dentist practise preventive dentistry today?


Chair-side fabrication of a duplicate denture.


Avoiding potential pitfalls in peer review.


Fluoride supplements for prophylaxis of caries.


Pit and fissure sealants.

Pit and fissure sealants.


A canadian's view of acupuncture.

A canadian's view of acupuncture.


A survey of odontogenic cysts and their relationship to squamous cell carcinoma.


[Letter: Time for positive action].

[Letter: Time for positive action].


Editorial: To see ourselves as others see us.


Staff handling of patient relations.

Staff handling of patient relations.


The rudder is back on the ship.

The rudder is back on the ship.


A practical emergency kit for the dental office.


Pulp responses to composite resins with or without Ca(OH)2 bases.


Recognition and control of emergencies in the dental office.


Maturation of membrane function: the permeability of the rat erythroblastic leukemic cell to water and to non-electrolytes. The erythroblastic leukemia produced in Long-Evans rats by the administration of 7, 8, 12 trimethylbenz (a) anthracene has been used as a model of the most immature form of the erythrocyte series. In conjunction with studies of the maturation of several other membrane functions, the permeability of this cell to water and to certain definitive non-electrolytes was measured with osmotic methods. The hydraulic conductivity, L-p was 6.2 micro (minute)-1, (atm)-1 at 25 degrees C, quite high and characteristic of mature erythrocytes, but different from values of 0.65 for immature myeloid cells. The effect of temperature provided an energy of activation of 4.4 kCal/mole, also typical of mature mammalian erythrocytes but again different from 13 to 18 kCal/mole for immature myeloid cells. Urea was compared to thiourea. The permeability coefficient for urea was 76.7 micra (minute)-1 plus or minus 13.8 (S. E.); the value for thiourea was 1.55 micra (minute)-1 plus or minus 0.18 (S. E.). Phloretin at 0.25 mM inhibited urea permeability by 90% with 50% inhibition occurring at 0.05 mM. Inhibition was reversible. Permeability to the glycols was also compatible with mature erythrocytes. We infer from these findings that the structure which underlies these basic, passive membrane functions is laid down early and persists after loss of nucleus and subsequent maturation.


Directional edgewise orthodontic approach. 5.


An in vitro evaluation of the particle flotation capability of various irrigating solutions.


Grading your orthodontic treatment results.


A combined fixed-removable approach to the treatment of impacted maxillary canines.


Transfer cases.

Transfer cases.


Delayed hyperphagia and increased body length after hypothalamic knife cuts in weanling rats. Four-week-old female rats received parasagittal hypothalamic knife cuts. Polydipsia began right surgery, but hyperphagia, obesity, and excessive nose-anal length did not begin until after the rats were 7-8 wk. old. The delayed onset appears to await some maturational event that is required for the expression of hypothalamic obesity. It appears likely that puberty is the critical maturational event.


Multiple knife cuts between the medial and lateral hypothalamus in the rat: a reevaluation of hypothalamic feeding circuitry. Single or multiple sets of bilateral knife cuts were made in female rats just lateral to the ventromedial hypothalamus (VMH) and/or just medial to the lateral hypothalamus (LH). The lateral VMH cuts by themselves produced greater hyperphagia and obesity than did the medial LH cuts. The lateral VMH knife cuts also significantly increased food intake and body weight in rats previously given bilateral cuts along the medial LH border. These findings indicate that the feeding inhibitory fibers responsible for the hyperphagia syndrome do not project from the VMH to the LH, and this calls for a reevaluation of hypothalamic circuitry. It was also discovered that sham surgery has a significant suppressive effect on the hyperphagia syndrome produced by hypothalamic knife cuts.


Modified cuspid retraction in Begg therapy.


The effect of cross-linking on indentation resistance, creep and recovery of an acrylic resin denture base material.


Mandibular posture and movement in edentulous individuals.


Comments on February guest editorial.

Comments on February guest editorial.


A comparative evaluation of the microhardness, water solubility and water absorption of fissure sealants.


Factor analysis of comprehensive examinations. In working toward new, integrated curricula, dental schools have often failed to concurrently revise their evaluative techniques to be more compatible with the objectives of the curriculum. One question of major importance is whether the schools are totally aware of their students' capabilities or are graduating students proficient in some fields while lacking in others. Is the student's overall or total score satisfactory even though deficiencies may exist in certain areas? This latter situation is a real possibility when the simple sum of subtest scores is used as the primary means in assessing students. Using factor analysis, the scores on the subtests of eight dental school comprehensive examinations (total of 1,023 subjects, on first-, second-, and third-year examinations given between December 1970 and May 1972) at the University of Pittsburgh School of Dental Medicine were examined. The results, culled from the correlation matrices, Chi-square analysis, and factor matrices, indicated that the subtests did not form a homogenous unit (one, general factor), and hence that use of the total score is questionable.


Molecular weight distribution of denture base acrylic.


Photoelastic studies in the edentulous human mandible.


Time versus performance quality in perceptual motor skills.


An experimental laboratory program in oral biology.


Correlates between cognitive and noncognitive factors in freshman dental students.


A study of the professional role satisfaction of dentists.


Editorial: Reciprocity--European style.

Editorial: Reciprocity--European style.


The study of joints in gross anatomy.

The study of joints in gross anatomy.


Future trends in dental education.

Future trends in dental education.


Letter: Analysis of the ADA Survey of Dental Practice.


Leadership and the professional ethic.

Leadership and the professional ethic.


Perspective on prevention.

Perspective on prevention.


Tumors of bone.

Tumors of bone.


Diagnosis please. Central giant cell reparative granuloma.


To be or not to be controlled.

To be or not to be controlled.


Statistical inferences about injury and persistence of environmentally stressed bacteria. A standard technique for ascertaining the survival characteristics of bacteria after being environmentally stressed is to incubate the bacteria on both selective and non-selective media and count the colonies produced. Based on these colony counts, indexes of injury and persistence of the bacteria are calculated. To compare the stress of two different environments, a persistence ratio is calculated. In this paper, methods of statistical inference concerning these indexes and ratios are presented. These statistical methods use well-known procedures for analysis of binomial data and 2 times 2 table data, and are appropriate when the colony counts follow a Possion distribution.


The evaluation of hypersensitivity tests in cattle after foot-and-mouth disease vaccination. The response to passive cutaneous anaphylaxis, dermal hypersensitivity and intravenous provocation tests has been compared in 30, 40, 31 and 24 cattle injected with foot-and-mouth disease vaccine 0, 1, 2 and 3 times respectively, using vaccine components and other substances as test materials. Reaginic antibodies demonstrated by passive cutaneous anaphylaxis in goats, were directed against BHK 21 cell extracts (20), hydroxypropylmethylcellulose (3) and an unidentified vaccine component (3), and distributed in 0, 5, 19 and 75 per cent of the cattle vaccinated 0, 1, 2 and 3 times. None of the animals showed clinical signs of allergy after vaccination. When BHK 21 cell extract was injected intradermally a significant correlation was noted between the development of large weals and the presence of reagins although the size of the weals was not correlated with the reagin titres. In the case of hydroxypropylmethylcellulose a similar trend was evident. The majority of cattle with large dermal weals possessed reagins but the number of reactions was too small for statistical evaluation. Dermal reactions to sodium penicillin, sodium carboxymethylcellulose, saponin and whole vaccine occurred in both unvaccinated and vaccinated cattle but BHK 21 cell lysate and normal bovine serum provoked weals which increased in frequency according to the number of vaccinations experienced. Intravenous hydroxypropylmethylcellulose elicited a response in all the animals previously injected with certain batches of vaccine but cell extract intravenously produced a clinical response in half the tested animals which was uncorrelated with the results of the passive cutaneous anaphylaxis or dermal hypersensitivity tests.


Outbreaks of bovine salmonellosis caused by serotypes other than S. dublin and S. typhimurium. Outbreaks of salmonellosis caused by serotypes other than S. dublin and S. typhimurium were investigated on 41 farms in north-west England. Of these, 37 (90 per cent) were in dairy cows. There was strong circumstantial evidence that contaminated dairy cake was the source of infection in at least four herds and probably many more. Twenty-six serotypes were encountered with S. newport, the commonest, causing the most severe disease. Most cattle seemed to rid themselves of infection during the following months whether or not they were at pasture, housed in cubicles or in byres. Some cows excreted salmonellas for up to 11 months after the disease outbreak. Associated human salmonellosis was confirmed on 3/41 (7 per cent) of the farms.


Counter-electrophoresis as a possible method for typing ECHO and Coxsackie B viruses. A method for typing ECHO and Coxsackie B viruses using counter-electrophoresis has been developed using stock strains of 15 different ECHO types and 5 Coxsackie B viruses. Work is continuing to see whether the method is a practical one to use for typing of strains from patients infected with ECHO or Coxsackie B viruses.


The role of wild ruminants in the epidemiology of bovine petechial fever. After experimental inoculation of Cytoecetes ondiri, the agent of bovine petechial fever (BPF), multiplication occurred in impala, bushbuck, Thomson's gazelles and wildebeest, as shown by infectivity studies and clinical findings. Similar attempts to infect one eland failed. As a sequel to this, blood and spleen samples were collected from four species of wild ruminants in an area where BPTF was endemic. Isolations of C. ondiri were made from three of five bushbuck, but not from any other species.


Response to influenza vaccine in adjuvant 65-4. A comparison was made of the antibody response and subjective reactions to zonally-purified influenza vaccine in aqueous suspension and in peanut oil adjuvant 65-4. Both preparations contained 700 CCA units of A/Aichi/2/68, and 300 CCA units of B/Mass/1/71. Subjective reactions were recorded by asking the volunteers to complete a record daily for 5 days. Pain at the injection site was recorded by 64 per cent of the recipients of the oil adjuvant vaccine compared with 35 per cent of the aqueous recipients, but local redness was more frequent after aqueous vaccine. Systemic symptoms was recorded a little more frequently after aqueous than oil adjuvant vaccine. When measured 71/2 weeks after a single dose of vaccine, the HAI geometric mean antibody titre (G.M.T) to the A/Hong Kong/1/68 antigen (antigenically similar to the A/Aichi/2/68 antigen in the vaccine) increased 2-7 fold after aqueous and 16-4 fold after adjuvant vaccine. Sixty-two weeks after vaccination the antibody titres remained higher in those given adjuvant vaccine. The G.M.T. to B/Mass/1/71 increased 1-9 fold 71/2  weeks after aqueous vaccine and 3-7 fold after adjuvant vaccine. The antibody response to both influenza A and B antigens was broader in the recipients of adjuvant vaccine. The G.M.T. to A/England/42/72 increased 2-8-fold after aqueous and 13-fold after adjuvant vaccine; and to B/England/847/73 it increased 1-3-fold after aqueous and 1-9-fold after adjuvant vaccine.


Presence of a dialysable fraction in normal bovine whey capable of killing several species of bovine mycoplasmas. Most normal bovine whey samples contain a fraction that survives heating at 56 degrees C. for 30 min., passes through a dialysis membrane and kills a maximum of seven out of ten of the different bovine mycoplasma species tested. Some whey samples appear more active than other but not all affect the same strains of mycoplasma indicating some specificity in their action. Absorption of the active factor from whey by heterologous and homologous mycoplasmas and by erythrocytes was observed. Binding of the factor to mycoplasmas appears to be temperature-dependent and non-specific, but subsequent mycoplasmacidal action shows some specificity.


Trends in salmonella food poisoning in England and Wales 1941-72. Cattle and pig herds and flocks of domestic fowl have formed the main reservoir of human salmonella food poisoning in England and Wales from 1941 to 1972. Changes in the incidence of human salmonella food poisoning and in the serotypes of salmonellas isolated from human infections are shown to have been associated with the introduction of new foods, with changes in animal husbandry, and with changes in the relative proportions of flesh food from different species consumed. New foods, dried powdered egg, liquid egg and frozen liquid egg were introduced during the period of food rationing which extended from 1940 to 1953. Changes in animal husbandry, in particular the intensive production of pigs, poultry and eggs, followed the re-establishment of pig herds and fowl flocks after the derationing of animal feed in 1953. The changes in the proportions of flesh foods consumed followed the introduction of frozen oven-ready fowl in the late 1950s and early 1960s which by 1964 became cheaper than traditional flesh foods.


Experiences with EDDA's.

Experiences with EDDA's.


Abreviated periodontal examination.

Abreviated periodontal examination.


Famous dentists.

Famous dentists.


An analysis of the sargenti method. Part 1.


Dentigerous cyst decompression.

Dentigerous cyst decompression.


Successful patient motivation.

Successful patient motivation.


Pterygoid extension implant.

Pterygoid extension implant.


MPD. Bio-feed back technqiue in treating myo-facial pain disfunction syndrome.


Suture splint for displaced teeth.

Suture splint for displaced teeth.


Burkitt's tumor in New Jersey: A portrait.


The issue of ethics.

The issue of ethics.


Your dental practice act and state board of dentistry.


Orthodontic vs. restorative treatment of the congenitally absent lateral incisor--long term periodontal and occlusal evaluation.


Host tissue response in chronic inflammatory periodontal disease IV. The periodontal and dental status of a group of aged great apes.


The nature of healthy and diseased root surfaces.


The role of IgE in the release of histamine from human gingival mast cells. Twelve gingival samples removed from 6 human volunteers were sectioned in small pieces, parts of which served as uncultured pieces. The remaining pieces were organ cultured for 5 hours in control, compound 48/80, and antihuman IgE media. Uncultured tissues, cultured tissues, and cultured spent media were analyzed spectrofluorometrically for histamine content. The uncultured tissues contained a mean (plus or minus SE) of 5.41 plus or minus 0.60 mug/g of histamine and were considered to contain 100 percent total histamine. The percentage of the total histamine released into the medium was 8.24 percent for cultured control, 56.7 percent for antihuman IgE, and 66.7 percent for compound 48/80. Significant histamine release into medium was noted for antihuman IgE (P less than 0.0005) and for compound 48/80 (P equals 0.005), but these two were not significantly different from each other (P greater than 0.25). Significant tissue histamine reduction was recorded for tissues cultured in compound 48/80 (P less than 0.025), whereas a significant tissue histamine synthesis was demonstrated for tissues cultured in antihuman IgE (P less than 0.05). The control tissues revealed neither significant histamine release into the medium nor significant tissue histamine reduction or synthesis. The results demonstrate IgE in clinically healthy human gingiva, show its association with gingival mast cell histamine release, and establish an in vitro model system for further human mast cell study. Thus, the concept of an association between IgE antibodies and human gingival mast cells is supported.


Potentiation of 5-fluorouracil with occlusive dressing.


Further observations on the gingival cyst. Three case reports. Three clinically discernable gingival cysts have been described and documented histologically. Two of these lesions occurred in the same patient in adjacent areas of the mouth. The potential origin of such cysts has been described. We suggest that gingival cysts are not clinical curiosities, as proposed in earlier reports.


Time trends in survival in acute lymphocytic leukemia. Comparison of patients under 20 years of age with acute lymphocytic leukemia diagnosed in 1955-64 with those whose disease was diagnosed in 1965-69 revealed a marked improvement in median survival time, from 9.5 to 16.8 months. This improvement occurred among patients with less favorable hematologic and symptomatic characteristics as well as among patients with more favorable ones. However, a shift in patient characteristics was consistent with the concept of diagnosis earlier in the natural history of the disease. In the more recent period, fewer patients were classified as severely disabled, and a somewhat higher proportion were in more favorable categories with respect to platelet count, percent of polymorphonuclear leukocytes, organomegaly, and bleeding or infection. Initial treatment was markedly different during the two time periods; this reflected a shift toward the use of combinations of chemotherapeutic agents and steroids.


Cyanoacrylate as a periodontal dressing.


Neurilemmoma of the tongue.

Neurilemmoma of the tongue.


Is methotrexate therapy for psoriasis carcinogenic? A modified retrospective-prospective analysis. The use of methotrexate in psoriasis has recently been questioned because of possible carcinogenic potential. Two hundred twenty-four patients began methotrexate therapy during 1960 to 1965 at the Cleveland Clinic and at Duke University Medical Center. The incidence of malignant neoplasms and mortality has been studied in 205 of these 224 patients. Mortality increased with hepatic disease. No increased incidence of total internal malignancy was found, nor did any one type of neoplasm appear predominant.


Agglutination of leukemic and 2,4-dinitrophenyl-tagged normal human lymphocytes by wheat germ agglutinin. The present study was undertaken to determine if leukemic and 2,4-dinitrophenyl (DNP)-tagged normal human lymphocytes shared common receptors for Wheat Germ Agglutinin (WGA), a lectin capable of reacting with malignant cells. Normal peripheral blood lymphocytes were tagged with 2,4-dinitrofluorobenzene (DNFB) at a ratio of 10-11 molecules/cell. Various concentrations of WGA were added to leukemic or tagged or untagged normal lymphocytes and incubated for 20 minutes at 37 degrees C, after which agglutination was scored visually. A readily discernible quantitative difference in the agglutinability of leukemic and DNP-tagged versus untagged normal cells was seen at all concentrations of WGA in the range of 50-800 mug/ml. The reaction was maximal when a ratio of 10-11 molecules of DNFB/cell was used for tagging and decreased progressively with 10-8, 10-6, 10-4, 0r 10-2 molecules. The agglutination of leukemic and DNP-tagged normal lymphocytes by 200 mug/ml of WGA was completely blocked by 0.1 M N-acetylglucosamine (GlcNAc) while as low a concentration as 0.001 M GlcNAc inhibited the reactivity of untagged cells. Since the agglutination of leukemic and DNP-tagged normal lymphocytes was equally inhibited by GlcNAc, this suggests that the same or similar receptor sites were involved in the two reactions. On the basis of our observations we propose that the initial step in the agglutination of leukemic and DNP-tagged normal lymphocytes by WGA IS THE BINDING OF THE LECTIN TO SPECIFIC RECEPTORS RATHER Than to DNP residues on the cell surface, since leukemic cells tagged with DNFB did not show increased agglutinability.


Maternal deaths in South Carolina 1961-1971.


Selectivity of proteinuria: origin of the proteins and potential diagnostic aid.


Propranolol: another view.

Propranolol: another view.


President's pages.

President's pages.


Editorial: Image--MUSC.

Editorial: Image--MUSC.


Acute Monteggia lesions in children.

Acute Monteggia lesions in children.


Admission to medical school.

Admission to medical school.


Hysteroscopy.

Hysteroscopy.


Rural health delivery--an impossible dream?


Editorial: A method to solve the doctor shortage.


Inaugural address, Charleston County Medical Society.


Delivery vehicles: leasing vs. purchasing.


Varied response to injury and to endodontic treatment.


Health services research and dentistry.

Health services research and dentistry.


The Academy of General Dentistry.

The Academy of General Dentistry.


Intra-aortic balloon counterpulsation in acute cardiogenic shock.


Lidocaine topical film strip for oral mucosal biopsies.


Mediastinoscopy in the assessment of operability of bronchogenic carcinoma.


Lateral periodontal cyst: report of a case.


Editorial: Drug utilization review.

Editorial: Drug utilization review.


Abnormal renal urate homeostasis in systemic disorders. Abnormalities of renal handling of urate occur in a wide variety of physiological and pathological conditions and are mediated by factors including renal blood flow, glomerular filtration rate, urine flow rate, urinary constituents, metabolites, hormones and drugs. The determination of the aetiological factors in each abnormal situation is complex and the problem is discussed in relation to a variety of conditions including renal tubular disorders and mental intoxications, hypertension, toxaemia of pregnancy, glycogen storage disease, fructose administration, hereditary fructose intolerance, as well as obesity, regular alcohol consumption and hyperlipoproteinaemia. Apart from those diseases, usually genetically determined, which are associated with excessive production of urate, the most common causes of hyperuricaemia act at a renal level and result in a reduction in the net renal excretion of urate.


Treating depression with tranquilizers: with dissenting view of lithium carbonate therapy.


Correlation conferences in radiology and pathology: Vague abdominal pain and change in bowel habits.


Giant-cell carcinoma of breast.

Giant-cell carcinoma of breast.


New HMO law. PL 93-222.

New HMO law. PL 93-222.


Diversion of narcotic and stimulant drugs.


Peer review and the anesthesiologist.

Peer review and the anesthesiologist.


Welfare recipients as paraprofessionals; utilization in facility for retarded patients.


Neighborhood drug treatment centers; opposition to establishment: problem in community medicine.


Permanent tooth pulpotomy--report of a case.


Editorial: Ecological odontology.

Editorial: Ecological odontology.


Editorial: Health and the senior citizen.


A program for community preventive dentistry.


Editorial: For approval, a revised constitution.